Retinal Structures and Visual Cortex Activity are Impaired Prior to Clinical Vision Loss in Glaucoma

Abstract

Glaucoma is the second leading cause of blindness worldwide and its pathogenesis remains unclear. In this study, we measured the structure, metabolism and function of the visual system by optical coherence tomography and multi-modal magnetic resonance imaging in healthy subjects and glaucoma patients with different degrees of vision loss. We found that inner retinal layer thinning, optic nerve cupping and reduced visual cortex activity occurred before patients showed visual field impairment. The primary visual cortex also exhibited more severe functional deficits than higher-order visual brain areas in glaucoma. Within the visual cortex, choline metabolism was perturbed along with increasing disease severity in the eye, optic radiation and visual field. In summary, this study showed evidence that glaucoma deterioration is already present in the eye and the brain before substantial vision loss can be detected clinically using current testing methods. In addition, cortical cholinergic abnormalities are involved during trans-neuronal degeneration and can be detected non-invasively in glaucoma. The current results can be of impact for identifying early glaucoma mechanisms, detecting and monitoring pathophysiological events and eye-brain-behavior relationships, and guiding vision preservation strategies in the visual system, which may help reduce the burden of this irreversible but preventable neurodegenerative disease.

Optic Radiations Microstructural Changes in Glaucoma and Association With Severity: A Study Using 3Tesla-Magnetic Resonance Diffusion Tensor Imaging

“…Finally, functional MRI may offer new insights into the brain modifications associated with glaucoma, as suggested by two recent studies, showing functional modifications of the visual cortex at the earliest stages of the disease. 47,48 In conclusion, we confirmed microstructural changes of optic radiations in glaucoma and its association with glaucoma severity. In accordance with several other studies, DTI appears as an objective measurement for evaluating alterations of the visual pathways in glaucoma and provides new insight in the pathophysiological process of glaucoma.…”

“…For instance, in a recent study by Frezzotti et al, 21 only severe cases of glaucoma (but not early) showed gray matter atrophy of the visual cortex and hippocampus. 47 The evolution of brain volume in the course of glaucoma and its association with other neurodegenerative diseases would need further investigation and prospective follow-up of subjects. Finally, functional MRI may offer new insights into the brain modifications associated with glaucoma, as suggested by two recent studies, showing functional modifications of the visual cortex at the earliest stages of the disease.…”

Structural and functional correlates of visual field asymmetry in the human brain by diffusion kurtosis MRI and functional MRI

“…Future studies should include a larger population and encompass a greater age range to determine any age-dependent effects on visual field asymmetry in the brain. This may also provide clinical relevance because of the increasing aging population and age-related diseases that are susceptible to regional visual field loss in the brain such as glaucoma 23 . Additionally, the quantitative fMRI and DKI comparisons were based on the global average across activated brain regions for each type of visual field stimulations.…”

The Future of Imaging in Detecting Glaucoma Progression

“…Human eye studies have revealed the ability of fMRI to detect inner retinal layer thinning, optic nerve cupping and reduced visual cortex activity prior to any evidence of visual field impairment on SAP testing (79). Pursuing additional functional imaging techniques, researchers have also used proton magnetic resonance spectroscopy (MR spectroscopy) to assess cross sectional glaucoma diagnosis.…”

“…Pursuing additional functional imaging techniques, researchers have also used proton magnetic resonance spectroscopy (MR spectroscopy) to assess cross sectional glaucoma diagnosis. These methods have revealed a correlation between choline metabolism disruptions within the visual field and disease severity on diffusion tensor MRI and visual field assessment (79). Longitudinal studies with larger sample sizes are still needed before conclusions can be drawn about the clinical utility of these methods.…”